Renal Cell Cancer Update
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You are here: Home: RCCU 1 | 2008: Janice P Dutcher, MD

Dutcher, MD

Tracks 1-18
Track 1 Temsirolimus, interferon alpha or the combination as first-line therapy for poor-risk mRCC
Track 2 Potential mechanism of action of temsirolimus in RCC
Track 3 AVOREN trial: Interferon alpha-2a with or without bevacizumab as first-line therapy for mRCC
Track 4 Bevacizumab monotherapy and stable disease
Track 5 Challenges in evaluating combination biologic therapies in RCC
Track 6 Clinical algorithm for the treatment of mRCC
Track 7 Side effects and tolerability of interleukin-2
Track 8 Potential mechanisms of action of immunotherapy in RCC
Track 9 Use of bevacizumab monotherapy
Track 10 Dose adjustments and management of toxicity in patients undergoing targeted therapies
Track 11 Selection of second-line therapy in mRCC
Track 12 New developments in the management of TKI-associated hand-foot syndrome
Track 13 Dose reductions to manage TKI-associated toxicities
Track 14 Dose escalation of sorafenib in mRCC
Track 15 Ongoing adjuvant trials in RCC
Track 16 Use of chemotherapy for patients with rapidly progressing mRCC
Track 17 Case discussion: A septuagenarian with small, bilateral mRCC lung nodules and subsequent brain metastases with rapid symptom relief from sunitinib
Track 18 Management of the primary tumor in patients with concurrent mRCC

Select Excerpts from the Interview

Track 1

Arrow DR LOVE: Can you talk about the temsirolimus/interferon alpha data that were reported at ASCO 2006?

Arrow DR DUTCHER: The study of temsirolimus versus interferon versus the combination in patients with poor-risk renal cell cancer was initially presented at ASCO 2006 (Hudes 2006, 2007; [4.1, 4.2]). The poor-risk features were based on criteria from Sloan-Kettering (Motzer 2002) and included nephrectomy status, high serum lactate dehydrogenase levels, anemia, hypercalcemia and rapid time from diagnosis of primary RCC to mRCC and features that ref lected a likelihood of rapid disease progression.

The study demonstrated a significant improvement in progression-free survival and overall survival for temsirolimus compared to interferon (4.1). This finding suggests that in patients with poor-risk disease, immunotherapy cannot catch up to the disease process, whereas targeting a different pathway might be effective.

We went back and evaluated the data, and a significant number of patients did not have clear cell renal cancer (Dutcher 2007). These patients had different histologies, mostly papillary or undifferentiated mRCC, and they benefited from temsirolimus significantly more than from interferon, which supports our belief that immunotherapy is not as effective in nonclear cell mRCC.

4.1

Tracks 6-7

Arrow DR LOVE: What factors do you take into consideration when deciding on first-line therapy in the metastatic setting for clear cell RCC?

Arrow DR DUTCHER: We still administer high-dose interleukin-2 to patients who seem likely to respond to this therapy, and some patients have durable complete responses lasting several years.

My own approach is to screen patients to determine whether they are candidates for high-dose interleukin-2 and discuss that therapy along with targeted therapy options. If possible, I prefer to enter patients on a clinical trial for firstline therapy in the metastatic setting.

In cases for which we need tumor shrinkage right away — for example, an endobronchial tumor that’s causing atelectasis — sunitinib would be more effective because its shrinkage rate is higher than other first-line options.

At present we do not have a lot of information on first-line temsirolimus. However, based on the available data, it would be a good choice for patients with poor-risk disease (Hudes 2007).

Arrow DR LOVE: Interleukin-2 is typically considered for use in younger, healthier patients. Is this your practice?

Arrow DR DUTCHER: I base my decision on physiology as opposed to age. The patients I encourage to receive interleukin-2 are those with lung-only metastasis and good pulmonary and cardiac function. I treat patients in their late sixties or early seventies who have fairly limited metastatic disease.

For patients with rapidly growing disease, I do not use immunotherapy. Those patients need targeted therapy because it provides a better chance to stop the disease. Interleukin-2 is more appropriate for patients with more typical, slowgrowing, indolent mRCC.

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